Document Type : Original Article
Authors
1
Cell and Molecular Research Centre, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2
Department of Physiology, Physiology Research Centre, Research Institute for Infectious Diseases of the Digestive System, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3
Department of Bone Marrow Transplantation, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
5
Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran ;Department of Anatomical Sciences, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Abstract
Objective: One of the severe complications and well-known sources of end stage renal disease (ESRD) from diabetes mellitus is diabetic nephropathy (DN). Exosomes secreted from diverse cells are one of the novel encouraging therapies
for chronic renal injuries. In this study, we assess whether extracted exosomes from kidney tubular cells (KTCs) could prevent early stage DN in vivo.
Materials and Methods: In this experimental, exosomes from conditioned medium of rabbit KTCs (RK13) were purified by ultracentrifuge procedures. The exosomes were assessed in terms of morphology and size, and particular biomarkers were evaluated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Western blot, atomic force microscopy (AFM) and Zetasizer Nano analysis. The rats were divided into four groups: DN, control, DN treated with exosomes and sham. First, diabetes was induced in the rats by intraperitoneial (i.p.) administration of streptozotocin (STZ, 50 mg/kg body weight). Then, the exosomes were injected each week into their tail vein for six weeks. We measured 24-hour urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) levels with detection kits. The histopathological effects of the exosomes on kidneys were evaluated by periodic acid-Schiff (PAS) staining and expressions of miRNA-29a and miRNA-377 by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: The KTC-Exos were approximately 50-150 nm and had a spherical morphology. They expressed the CD9 and CD63 specific markers. Intravenous injections of KTC-Exos potentially reduced urine volume (P<0.0001), and 24-hour protein (P<0.01), BUN (P<0.001) and Scr (P<0.0001) levels. There was a decrease in miRNA-377 (P<0.01) and increase in miRNA-29a (P<0.001) in the diabetic rats. KTC-Exos ameliorated the renal histopathology with regulatory changes in microRNAs (miRNA) expressions.
Conclusion: KTC-Exos plays a role in attenuation of kidney injury from diabetes by regulating the miRNAs associated
with DN.
Keywords
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